反应详情

A mixture of 5,6-dichloronicotinic acid (356 mg), iodoethane (318 mg) and potassium carbonate (308 mg) in N,N-dimethylformamide (3 mL) was heated at eighty degree for fourteen hours. The mixture was allowed to cool to ambient temperature and to this was added (3R)-1-(cyclohexylmethyl)-3-piperidinamine dihydrochloride (549 mg) and potassium carbonate (898 mg) and heated at eighty degree for thirtyeight hours. The mixture was allowed to cool to ambient temperature and was added water. The mixture was extracted with ethyl acetate (100 mL) and aqueous phase was separated. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was filtered and evaporated in vacuo to give an amorphous solid. The crude solid was purified by a flash chromatography eluting with 3% methanol-chloroform (v/v) to give ethyl 5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}nicotinate (154 mg) as a pale yellow amorphous solid.

1. temperaturewas heated at eighty degree for fourteen hours
2. temperatureheated at eighty degree for thirtyeight hours
3. temperatureto cool to ambient temperature
4. extractionThe mixture was extracted with ethyl acetate (100 mL) and aqueous phase
5. customwas separated
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationThe solvent was filtered
9. customevaporated in vacuo
10. customto give an amorphous solid
11. customThe crude solid was purified by a flash chromatography
12. washeluting with 3% methanol-chloroform (v/v)